Using Caffeine to Optimize Mental & Physical Performance | Huberman Lab Podcast 101

0:00 ANDREW HUBERMAN: Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. [MUSIC PLAYING] I'm Andrew Huberman, and I'm a professor of Neurobiology and Ophthalmology at Stanford School of Medicine. Today we are discussing caffeine. Caffeine is one of the most widely used substances on the planet. Estimates are that more than 90% of adults and as many as 50% of kids that is adolescents and teenagers use caffeine on a daily basis. Caffeine is an amazing molecule. Most people are familiar with caffeine's ability to increase alertness and to reduce our feelings of sleepiness and fatigue. And indeed, it does that. But what most people are not aware of is that caffeine acts as a strong reinforcer.

0:47 What I mean by reinforcer is that, when caffeine is present in a drink or food-- and yes, indeed, caffeine is present in many foods even unbeknownst to us. When it's present in drinks and foods, we actively come to like those foods and drinks more than if caffeine were not contained in those foods and drinks. So it reinforces our liking of particular foods and drinks. And indeed, it even reinforces our liking of the containers they are consumed from and the company we keep when we consume foods and drinks that contain caffeine. That is, caffeine is not just a stimulant. Caffeine is a reinforcer. And it's a reinforcer that plays an active role in almost everybody's daily life. We can say that with confidence because, as I mentioned

1:34 a moment ago, more than 90% of people are consuming caffeine. And most people think that they consume caffeine because it makes them feel more alert. But there are many reasons why you're consuming caffeine. And I'm not going to tell you that consuming caffeine is necessarily bad. In fact, today, I'm going to tell you about many of the positive health benefits of caffeine, including neuroprotective effects, antidepressive effects, and certainly performance-enhancing effects, both for mental performance and for physical performance. Now that said, there are certain situations in which you want to avoid caffeine, and there are certain people who might opt to avoid caffeine. That's especially the case when one thinks about caffeine not just as a stimulant but as a reinforcer. In fact, caffeine is such a strong reinforcer that, if even tiny amounts of caffeine are present in certain foods and drinks,

2:20 you will very quickly come to prefer those foods and drinks over other choices, which can be a good thing or a bad thing, depending on what sorts of food and drink choices you're trying to make. So today, I'm going to inform you about how caffeine works at a mechanistic level. I promise to do that with a minimum of nomenclature and such that, even if you don't have a background in biology, you will be able to digest that information easily. And then I'll tell you how to use caffeine to your advantage or conversely how to avoid caffeine at certain times to your advantage. So today's episode will focus both on mechanisms and tools that is the use and leverage of caffeine to improve mental health, physical health, and performance. Before we go any further into today's discussion, I want to tell you about some recent results about a molecule that's found in certain caffeinated beverages

3:07 and that has been proven to be very useful for both weight loss, mental performance, and controlling blood sugar levels. And that's GLP-1 or glucagon-like peptide 1. Glucagon-like peptide 1 is found in the brain and body. It acts both on the brain and body. It does many different things. But one of its primary effects that's been discovered is to reduce hunger. And it does that in two ways. It does that by activating certain neurons in your hypothalamus. So that's a brain region that controls hunger and satiety. It makes us feel full at the level of the brain, so it makes us feel sated, that is. And it actually makes us feel full. It turns out that GLP-1 acts on certain receptors in the gut to make us feel as if we've ingested enough food. It doesn't necessarily make us feel as if our gut is distended, but it makes us feel full.

3:54 That's really interesting because, if you think about it, when we eat, our stomach fills up, obviously. And that information has to be communicated to the brain such that the brain can then send satiety signals that actually shut off our hunger. And believe it or not, the brain actually activates signals to reduce the desire to chew when our stomach is full. And GLP-1, as I mentioned, works on the brain to create these feelings of satiety as if we've had enough and to reduce our desire to eat more. And GLP-1 acts directly on the gut to give us a slight sense of fullness in the gut, which then is communicated to the brain. So really, there are two parallel signals being sent when we have GLP-1 present in our system. Now a little bit of relevant history on GLP-1. It was actually discovered in Gila monsters. These are these reptiles that can go long periods of time

4:41 without eating. And a very clever scientist decided to study why it is that certain animals like Gila monsters can go a long period of time without ingesting anything. And it's because they produce very large amounts of GLP-1. They isolate the peptide from GLP-1, then they looked for the analogous peptide in humans. And it turns out that does exist. And as I mentioned, it's released in both brain and body to make you feel full and sated. Why am I telling you all this? Well, today we're going to talk about caffeine. And there's one particular caffeine source, which is yerba maté, and there are some other forms of teas similar to yerba mate that stimulate the release of GLP-1 significantly. There are also nowadays drugs which are called analogues of GLP-1. So these are drugs that mimic or are

5:27 identical to the kind of GLP-1 that you would make. And those drugs are proven to be very effective for the treatment of certain forms of diabetes and for the treatment of obesity, but they trigger enormous amounts of GLP-1 pathway activation. So those are extreme cases for people that are really struggling for weight loss. But the clinical trials and the data that are out there in the general population now are very, very promising for GLP-1 analogues. Yerba maté tea, provided it's not the smoked variety-- and I mention that because a number of people have cued me to the fact that yerba maté teas come in smoked varieties and nonsmoked varieties. And the smoked varieties are thought to perhaps be carcinogenic. That is, procancer-causing. So I advise people to avoid smoked varieties of yerba maté tea. But yerba maté teas are known to stimulate significant amounts

6:14 of GLP-1 release. And so they can be effective as a weight loss tool, mainly by blunting appetite. And again, they do that both at the level of the brain and at the level of the gut. Now all of what I just told you has been known for some period of time, but there are new set of findings that were just published in Cell Reports Medicine, Cell Press journal, excellent journal-- which indicate exactly how it is that GLP-1 stimulates both satiety and can trigger additional weight loss through other mechanisms. And I find the mechanism to be really interesting and actually really important, given some other topics we've covered on this podcast before. So the basic finding is that GLP-1, whether or not it's stimulated through the release of analogue drug that one is prescribed or by drinking yerba maté tea,

7:00 for instance, and stimulate release of your own so-called endogenous GLP-1, yes, it makes you feel more full at the level of brain and body. But it turns out it also stimulates thermogenesis. Now thermogenesis is the active utilization of more metabolic energy. And fat cells, in particular-- so-called beige and brown fat cells-- are a potent source of thermogenic activity in your body. The basic background is that you have white adipose cells, so white fat cells. You have beige fat cells, and you have brown fat cells. And the beige and brown ones are fat cells that you actually want more of. They are not abundant under your skin. They're abundant really around your clavicles and your upper neck. They are the ones that generate heat. And the beige and brownness of them

7:45 is actually the consequence of having a lot of mitochondria in those cells. When GLP-1 is elevated in your system, it turns out that it communicates to those white fat cells and helps convert them into beige and brown fat cells. That is, it takes fat cells that are not doing anything useful for you except being stored energy. And I think most people out there would like to have fewer of those white adipose cells. There are few of you out there that actually need more of them that are too thin, too lean, but most people are suffering from having too many of these white adipose cells. Well, when you ingest yerba maté tea or you were to take a GLP-1 analogue or stimulate GLP-1 in any number of different ways, yes, you stimulate increased satiety, but you're also stimulating the conversion of these white fat cells into beige and brown fat cells,

8:33 which makes you more thermogenic and over time raises your basal metabolic rate. So you're burning more calories even at rest. It also makes you feel as if you're more comfortable in colder environments at rest. This is very much the same as the mechanism that's induced when you were to, say, take a cold shower or do regular ice baths or get into cold water regularly. That, too, stimulates the conversion of white fat cells to beige and brown fat cells. So I like these findings very much because they provide a mechanistic coherence. They provide that is a really nice story as to how something like GLP-1 could be so effective for weight loss. Yes, on the one hand, GLP-1 is reducing appetite, and that, of course, will help people maintain or lose weight. But it's also increasing basal metabolic rate.

9:20 And we now know how that's accomplished. It's likely accomplished at least through this one mechanism by the stimulation of conversion of these white fat cells, which don't do much for us except as energy storage units to these metabolically mitochondrial-rich beige and brown fat cells, which you can think of as sort of the oil in the candle that allows your furnace, your metabolism to burn at a higher temperature and a higher rate. So that's the mechanism. And the basic tool takeaway is that, if you are somebody who's interested in losing weight and you want to leverage the GLP-1 pathway, drinking a cup or two of yerba maté tea early in the day would be a great way to stimulate GLP-1 release. There are other ways to stimulate GLP-1 release. You can get it through certain forms of exercise. In particular, fasted exercise.

10:05 This is actually a vote in favor of fasted exercise. There's a debate as to whether or not fasted cardio burns more fat than nonfasted cardio. And the data basically say no, it doesn't really matter. But that doesn't really take into account the longer arc of things like GLP-1 release, so that needs to be taken into consideration. So you could do fasted cardio. You could drink yerba maté tea, keeping in mind that yerba maté tea does contain caffeine. We'll talk more about the specific forms of stimulants including caffeine that maté has. But maté would be a great way to stimulate GLP-1 release. And then, of course, for those of you that are interested in more robust activation of GLP-1, then perhaps you might want to consider some of the new prescription GLP-1 analogues that are out there. But that's a more severe stimulus for GLP-1, of course. And for everybody, regardless of whether or not you're trying

10:51 to lose weight, gain weight, or maintain weight, I think we're going to be hearing a lot more about GLP-1 analogues and drinks and supplements and things of that sort that stimulate GLP-1 in the very near future because it does appear to be a very important biological mechanism. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Levels. Levels is a program that lets you see how different foods affect your health by giving you real-time feedback on your diet using a continuous glucose monitor. The blood glucose or blood sugar is a critical aspect of your immediate and long-term health and, indeed,

11:36 your feelings of vigor and mental clarity and well-being at any moment. One of the key things is to know how different foods and food combinations and timing of food intake is impacting blood glucose. And with Levels, you're able to assess all of that in real time. I tried Levels, and what it taught me, for instance, was that I can eat certain foods at certain times of day. But if I eat them at other times a day, I get a blood sugar crash. It also taught me, for instance, how to space my exercise and my food intake. Turns out for me exercising fasted is far more beneficial. That's something I learned using Levels, and it's completely transformed not just the spacing and timing of my diet and exercise but also use of things like the sauna and other activities. It's been a tremendous learning for me that's really shaped an enormous number of factors in my life

12:23 that have led to me feeling far more vigorous with far more mental focus and physical strength and endurance. So if you're interested in learning more about Levels and trying a continuous glucose monitor yourself, go to levels.link/huberman. Again, that's levels.link/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep make smart mattress covers with cooling, heating, and sleep-tracking capacity. I've talked many times on this podcast about the critical relationship between sleep and body temperature. That is, in order to fall asleep and stay deeply asleep throughout the night, our body temperature needs to drop by about 1 to 3 degrees. And conversely, when we wake up in the morning, that is in large part because of our body heating up by 1 to 3 degrees. Now people have different core body temperatures,

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13:56 that are of the absolute highest quality. The company was founded by two all-American swimmers from Stanford. And everything about ROKA eyeglasses and sunglasses were designed with performance in mind. I've spent a lifetime working on the biology, the visual system. And I can tell you that your visual system has to contend with an enormous number of challenges in order for you to see clearly, for instance, when you move from a sunny area to a shady area and back again, whether or not you're looking at something up close or often to the distance. ROKA understands the biology of the visual system and has designed their eyeglasses and sunglasses accordingly, so you always see with perfect clarity. ROKA eyeglasses and sunglasses were initially designed for activities such as running and cycling. And indeed, they are very lightweight. Most of the time I can't even remember that they're on my face. They're so lightweight. But the important thing to know about ROKA eyeglasses and sunglasses is that, while they

14:42 can be used during sports activities, they also have a terrific aesthetic, and they can be used just as well for wearing to work or out to dinner, et cetera. If you'd like to try ROKA eyeglasses and sunglasses, you can go to ROKA. That's R-O-K-A.com and enter the code Huberman to save 20% off on your first order. Again, that's Roka, R-O-K-A, dot com and enter the code Huberman at checkout. The Huberman Lab podcast is now partnered with Momentous supplements. To find the supplements we discuss on the Huberman Lab podcast, you can go to livemomentous, spelled O-U-S, livemomentous.com/huberman. Huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman. Let's talk about caffeine. So as I mentioned earlier, caffeine is consumed by basically most all adults every single day

15:30 and consumed at very regular times each day. In fact, if you were to take a look at your caffeine intake or the caffeine intake of somebody close to you, what you would realize is that they don't do so well if their caffeine intake arrives even 10, 20, or 30 minutes past their expected or usual intake of caffeine. That's pretty remarkable, and it brings to mind ideas that we are all, quote unquote, "addicted to caffeine" or that caffeine is somehow bad. I'm certainly not going to make the argument that caffeine is bad. First of all, I'm a regular caffeine user. I wouldn't call myself a caffeine abuser, but I am a regular caffeine user. And caffeine is known to have certain health benefits. I listed off a few of them earlier, but I'll mention those again now before going forward.

16:17 Caffeine is known to have certain neuroprotective effects. And that is because of its ability to increase neuromodulators, such as dopamine, but also other so-called catecholamines like norepinephrine. If you don't know what those names mean, these are molecules that increase levels of alertness, motivation, and drive. And so then therefore not surprisingly the large scale analyses of the relationship between depression and caffeine shows that, provided people are not drinking so much caffeine, that it makes them overly anxious, that regular intake of caffeine is inversely related to levels of depression. So it may have some antidepressant effects. And those could be direct or indirect. What do I mean by that? Well, you can imagine that if people are ingesting caffeine and they are more motivated to do work and pursue quality social interactions, then

17:03 the probability that they will have depression could be lower. It could also be that there are direct effects on the chemical systems of the brain that relate to mood and well-being that could offset depression. It is not clear whether or not the effects of caffeine in countering depression are direct or indirect. Nonetheless, there's a relationship there, and it's an interesting and positive one. Or I should say negative correlation, positive effect overall on mood and well-being, to be exact. Now it's also the case that caffeine can improve mental performance and physical performance. This has been demonstrated in tens of thousands of studies. I will review a few studies on this, in particular, today. But to just give you a sense of how caffeine works at the level of its timing and impact on mental performance and physical performance, when

17:51 we ingest caffeine, provided that we don't have a lot of food in our stomach and that our blood sugar isn't particularly high, generally, we experience an increase in alertness within about five minutes. And that increase in focus and alertness peaks around 30 minutes after ingestion of caffeine and persists for as long as 60 minutes. Now this is assuming that one takes caffeine in pill form or drinks the entire caffeine drink within a short period of time. But a little bit later, I'll talk about how you can consume caffeine at regular intervals while doing mental work or physical work in a way that can further increase mental performance and physical performance. But let's just touch on what caffeine intake really does for mental performance and physical performance. Perhaps the most robust finding across all

18:36 of the studies that I've examined is that caffeine reduces our reaction time. That is, it improves our reaction time. It doesn't make it longer. It makes it shorter. So for instance, in a laboratory study where people were asked to hit a lever every time they hear a tone, you can greatly reduce the time between the tone and the pressing of the lever if people ingest caffeine about 30 minutes before they do that task. Now that seems like a trivial task, but this is also seen in the domain of sports performance and even in cognitive performance, where people have to arrive at a particular answer to a question. And the answer to that question has to be pulled from their memory banks within their brain, their hippocampus, for instance, a brain structure involved in memory. And if you are asking people, for instance, to remember the capitals of different states or cities

19:24 or to remember certain historical facts, they will do that at a particular rate. But if they've ingested caffeine within the hour prior, their ability to recall that information is much, much better. They are faster, and it does not appear that accuracy is reduced. In fact, in many cases, accuracy is enhanced. And that's because caffeine both works on the reaction time systems of the brain and body. I'll talk about the mechanisms for that in a little bit. But it also stimulates certain neurotransmitters and so-called neuromodulators within the brain and body that give the neural circuits in the brain that are associated with learning and memory a lower threshold to activation. What does that mean? That means that we are better able to access the brain circuitry involved in learning and memory

20:12 when we have a certain amount of caffeine circulating in our system. So this makes caffeine an incredible performance-enhancing compound. And I could give you tens of thousands of examples of this in humans. But before I do that, I want to just touch on what we know about the existence of caffeine in nature and what the existence of caffeine in nature and its effects on other animals tells us about what caffeine does in humans. Because as I alluded to earlier, what caffeine is doing for us is not just making us more alert, improving our memory, improving our reaction time, and so on. It's actually acting as a powerful reinforcer of experience. And it's acting as not just a powerful reinforcer of the caffeine-containing drink that we drink

20:58 but also the mug that it's contained in, plus the person that we might be sitting across from when we consume that caffeine, and so on and so forth. If it's a little bit hard for you to conceptualize what a reinforcer is and why I'm calling it a reinforcer, let me spell it out in three specific ways. We often hear about the word reward, and we think, OK, if we do certain things and we like the outcome, then those certain things are rewarded. Right? If we're doing something, we receive praise. The praise is the reward. And therefore, we are more likely to do that thing in the future. In fact, a lot of parenting is like that. And a lot of life is like that. However, when we hear the word reward, we often think about something that feels good to us. And certainly, if we've worked hard and we get some praise,

21:45 that's natural for the praise to feel good to us. Or for instance, if we work very hard and we get a certain outcome-- a trophy, a financial outcome, a degree outcome, recognition, et cetera-- all of those can act as rewards, but those are all conscious rewards. We are aware that they are happening. Reinforcers are a little bit different because the word reinforcement can apply to conscious rewards of the sort that I just described, but there are also many ways in which caffeine stimulates the release of chemicals in our body that act as reinforcers. But those reinforcers are subconscious. That is, we are not aware that they cause this preference for the activities that cause their release. So the study I'm about to describe beautifully,

22:32 I believe, encapsulates how is it that humans came to consume caffeine and why caffeine exists in nature and the powerful effects of caffeine as a reinforcing agent both in animals, insects, and in you and me. And the title of the paper is "Caffeine and floral nectar enhances a pollinator's memory of reward." Keep in mind that caffeine is made from plants. Some of you will say, duh, but I think some of us don't realize that the reason why there is caffeine in coffee is because coffee comes from a plant. It's a coffee bean, certain teas, which, of course, are plants that people brew. Caffeine is contained in those teas, such as yerba maté. Well, why would this bitter substance-- because, in fact, caffeine is quite bitter in high concentrations. Why would this bitter substance be something

23:18 that insects or animals would want to consume at all? It turns out that, in most plants, caffeine is present in small enough quantities that insects and other animals-- and in fact, we can't actually taste the caffeine. If I were to give you a little bit of pure caffeine, yes, it would be a stimulant for you, but you would say that it tasted awful. It's in a category of compounds that would strongly stimulate the bitter receptors on your tongue and would make you cringe and pucker and essentially walk away from whatever it is that contain that caffeine and from the experience that contain that caffeine. Well, in nature, caffeine is present in very low concentrations or is masked by other flavors within flowers, beans, and plants. And what this paper really points to

24:04 is that caffeine in nature is acting as a reinforcer for bees that are consuming different nectar. So the way that it works is that bees, of course, go from flower to flower, and they are consuming the nectar. They are bringing nectar and pollen back to the hive, and that provides critical nourishment for the bee colony. The bees are foraging in a way that includes information about color, in particular, ultraviolet color, things that we can't see but they can see, because they have different photoreceptors than we do. And what the study shows is that plants and nectars that contain very small amounts of caffeine are the preferred sources of food for bees. And the study is beautiful because they

24:51 were able to confirm that they could mask the caffeine taste. So they know that the bees are not preferring the taste of caffeine. But what they do is they pair caffeine with different food sources for the bees, then they remove the caffeine. And what they find is that the bees very strongly prefer flavors that contain caffeine, not because they could taste the caffeine but rather for the way that those caffeine-containing flavors made the bees feel. So how do those caffeine-containing flavors make the bees feel? The same way that they make you and I feel, a little bit more alert and thereby able to do more work. For the bee, the more work is the consumption of more food, which then has a further reinforcing effect. So what we're really talking about here is the fact that A, caffeine exists in nature, in plants.

25:40 It exists in concentrations that are very low, so low, in fact, that they are not detectable to the taste receptors of insects, and, in many cases, to the taste receptors of humans. And, of course, there can be high levels of caffeine in a plant. But if the plant also contains compounds that mask the flavor of caffeine, well then, those plants are going to essentially be even stronger reinforcers for the flavor of the plant, OK? So now we're talking about strong flavors plus strong neurostimulant effects of caffeine. And the most important point here is that all of these effects of caffeine are subconscious. It is not because the bee or you likes the taste of caffeine. In fact, most people, when they take their first sip of coffee, they find it taste bitter and kind of noxious.

26:26 They don't like it. You may not even remember that because it happened so long ago and because caffeine is such a strong reinforcer that very quickly you come to like the taste of coffee. You might even come to like the feeling of your mug in your hand. You might even come to like the smell of coffee and so on and so forth. And that's because caffeine stimulates the release of certain neurochemicals in the brain, in particular, dopamine and acetylcholine, two neuromodulators that increase our focus and alertness and our feelings of well-being. A little bit later, I'll tell you that caffeine stimulates the release of dopamine in a way that's very much distinct from the classical dopamine pathway associated with addiction and reward. In fact, we can think of caffeine as having a somewhat privileged access to the reward systems.

27:11 I'll give you a bit of a hint of where this is going. Caffeine stimulates the release of dopamine and acetylcholine not within the classic so-called mesolimbic reward pathway. That's just fancy nerd speak for the reward pathways of the brain. They're associated with things like sex and food and drugs of abuse, like cocaine and methamphetamine. But rather, caffeine seems to stimulate the release of dopamine in the parts of the brain that are associated with alertness and cognition, meaning the forebrain. This is very important. We have multiple dopamine systems in the brain and body, and caffeine seems to stimulate dopamine directly within the components of the brain that are associated with clarity of thought and well-being, but more so clarity of thought. Now, I'm also talking about caffeine as a strong reinforcer in that it makes you feel good overall.

28:01 And it does. And that suggests that it also taps into the more classic reward pathway. But it does that in a very interesting and frankly almost diabolical way. When we regularly ingest caffeine, it stimulates the increase in dopamine receptors at multiple sites throughout the brain but, in particular, within the reward pathways of the brain. So not the areas of the brain that are associated with focus and clarity of thought and cognition. It does that, but it is also increasing the level of dopamine receptors in the reward pathway. And what that means is that, for any dopamine that's released in response to a positive experience, social experience, or any number of the other things that can stimulate dopamine release, there are more receptors, more parking spots, if you will, for that dopamine to arrive at and to exert its increases in mood, increases in motivation,

28:51 and overall feelings of drive and excitement. So there are four ways that caffeine works that we need to understand. First of all, caffeine acts as a reinforcing agent. It increases the probability that you will return to and engage in a certain activity or consume a certain beverage or food. Second of all, caffeine increases dopamine and acetylcholine, which are both neuromodulators in the forebrain, which helps us improve our ability to think, to modify our rule sets. That is, to adjust our strategies for different social situations and mental demands and physical demands. And third, it increases the number and efficacy of dopamine receptors in the reward pathways of the brain.

29:36 That is, it makes things that would feel pretty good feel even better. And fourth, caffeine acts as an antagonist to adenosine, which offsets the sleepiness that we would otherwise feel from the accumulation of adenosine that occurs as we are awake for more and more hours throughout the day. So let's talk first about caffeine as a reinforcing agent. Again, this was first most beautifully demonstrated in this study on honeybees where the bees prefer nectars that contain caffeine. And that all makes perfect sense in terms of the ecology of bees and flowers that contain nectar. There's an advantage, at least in terms of adaptation, that the flower benefits because of distribution of things from the flower, which is good for the flowers and the bees benefit, because they're getting food. And so there's a kind of a symbiosis there.

30:24 But with humans, we're consuming caffeine-containing beverages for our sake. I don't think we have it in mind, nor do the bees have it in mind, frankly, that we're trying to preserve the plants that provide the caffeine. I think we would all suffer, or I should say 90% of adults would suffer greatly if all the caffeine-containing coffee and tea plants were gone, certainly. But most of us are not consuming coffees and teas and caffeine-containing foods because we're thinking about the plants they come from and we want to help those plants. We're thinking about how we want to help ourselves. And yet the point of the reinforcing effects of caffeine are that they are largely subconscious. We are not aware of them. Now you might say, no, that's not true. When I drink caffeine, it makes me feel really good. So I'm aware that it makes me feel good. In order to illustrate how reinforcement really works,

31:11 let me give you the counter example, which would be an aversive agent. So we have reinforcing agents and we have aversive agents. Let's say that there were compounds in nature that exist in plants that are aversive. And indeed, they are. And let's say that these compounds were present at such low concentrations that you couldn't taste them. Let's say you wake up in the morning and you go to your refrigerator and you open it up and you are thirsty, and so you reach for a nice rich red-containing beverage in a glass jar. Maybe it looks like cranberry juice or something of that sort. Or even a nice clear glass of water. It looks like a jug of water or a glass of water, and you drink that. Taste fine to you. Maybe even tastes great to you. And then let's say about 30 minutes later, you feel a little queasy, you feel a little off,

31:57 you feel like going back to sleep, you just don't feel very good. You don't know why, but your nervous system is a predictive machine, and it has a process in which it back integrates. Or I should say integrates backwards into your immediate experience that preceded that not so good feeling. We can reliably say that there is a much lower probability that the next day when you wake up that you would reach for that same beverage or for that same container even. And maybe if you're in a novel environment, maybe you're staying in an Airbnb or a hotel or something of that sort, you might even find that you don't really like the kitchen in which you consume that beverage in the first place. And you don't know why. And unless you got very, very sick the day before,

32:45 it's unlikely that you would have such a strong response that you would entirely avoid, for instance, water or glass jars containing liquids, et cetera. Let's say you went back to the refrigerator and you consume a beverage again and you just didn't feel so well, you felt less good than you normally would. Well, even without any ability to taste what's in that beverage and even without any understanding of what was happening to you at a conscious level, there is a very, very high probability that you will avoid drinking that particular beverage and certainly at that location and in the same volume in the subsequent days. That's just the way that aversive agents work. And they work by way of activating neurons in the gut that communicate with areas in the brain that give us this feeling of queasiness.

33:32 And for some of you hearing this, that pathway and that association with times in which you felt queasy and as if you wanted to vomit is so powerful that you might even be feeling some of that symptomology now. For certain people that's going to be increased salivation which precedes vomiting, we know that there's a class of neurons in the brain relate to an area called area postrema that actually stimulates vomiting. And if I keep talking about this, I'll probably feel like I want to vomit, so I'm going to move on from this in a moment. So when we ingest caffeine-containing beverages and foods, it's the exact opposite scenario as to what I just described. Caffeine, as a reinforcer, makes us feel slightly better or a lot better in the immediate minutes and hours after we ingest it.

34:18 So it's acting as a reinforcing agent not just while you are under the effects of caffeine but for the things that preceded the ingestion of caffeine, which is why you return again and again to caffeine-containing beverages, such as coffee and tea or maybe even foods that contain caffeine, even if the taste of those foods is not something that you would otherwise consider, especially delicious. In fact, most people when they take their first sip of coffee or tea or other caffeine-containing beverage, they find it to be very bitter. And that's not because of the taste of caffeine. It's because of the taste of the beverage itself independent of caffeine. However, when caffeine is present in there, they come to prefer that taste over most all tastes. In fact, they will, as I mentioned earlier, will invest a lot of financial resources and time and energy

35:05 to make sure that they get that beverage. What they're trying to make sure is not that they get that taste but that they get the caffeine. It is that positively reinforcing. And the taste therefore takes on new significance, new meaning, and we come to associate it as positive. And in fact, most of us, including myself, love the taste of espresso, love the taste of coffee, love the taste of yerba maté even if the initial taste, the very first time that we consume that beverage, was either neutral or negative. And that is all because of the reinforcing properties of caffeine. And then, of course, there are the more direct actions of caffeine. That is, the faster actions of caffeine. And just to list those off again very briefly so that you have them in mind going forward, caffeine also

35:50 increases the release of dopamine and acetylcholine, both of which are neuromodulators in the forebrain, which increases clarity of thought and your ability to rule switch, your ability to move from one context to another and change and understand the rules of engagement, social engagement, physical engagement, mental engagement, and so forth. And as I mentioned before, caffeine also increases the number of dopamine receptors in the reward pathway, such that any good thing that happens to you. Any positive experience that you have will have a more potent effect on your feelings of well-being. And last but certainly not least, caffeine acts as an adenosine antagonist. It reduces your feelings of lethargy and fatigue

36:37 and your desire to sleep by parking in the receptors for adenosine and not allowing adenosine to have its pro-sleepy, if you will, effects on your brain and body. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health.

37:24 And those probiotics and Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met. And it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman, and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera. And they'll give you a year supply of Vitamin D3K2. Again, that's athleticsgreen.com/huberman to get the five free travel packs and the year supply of Vitamin D3K2. I'd like to just briefly talk about adenosine and some of its molecular features. And again, if you don't have a background in biology, don't worry.

38:09 I promise to make this very clear to everyone. First of all, caffeine is what's called a methylxantine. It's a plant alkaloid. That's why caffeine itself is very bitter. Again, if I were to give you just the tiniest little bit of pure caffeine, you would find it to be extremely aversive. So these plants that have snuck small enough amounts of caffeine into them or that have masked the flavor of caffeine with other flavors such that bees and humans want to consume them, while we don't know what plants think, it does seem very diabolical and very clever in that we are seeking out these caffeine-containing plants, beverages, and foods even though caffeine itself is this alkaloid that is very, very bitter. Methylxantine-- that is caffeine--

38:54 binds to adenosine receptors. And there are really two types of adenosine receptors. There are these so-called A1 receptors and the A2 receptors. And they are present in different parts of the brain and body at different levels. We don't have to get too far into receptor subtypes. More importantly to understand is that adenosine makes us feel tired because of the way that it taps into the ATP pathway. The ATP pathway is central to energy production and feelings of overall energy in our brain and body in all cells and organ systems. When caffeine binds to adenosine receptors, it prevents adenosine from breaking down certain components of the energy production pathway. And the net consequence of that is increased cyclic AMP. So basically, when we ingest caffeine,

39:42 we are biasing our system towards the pro-energetic aspects of these cellular pathways. Now it's really important to understand that, in biology, even if you block a receptor or you prevent the activity of an enzyme and-- at least, in this case, you end up with more cyclic AMP, more energy. You're not really getting more energy. You're actually borrowing energy against an overall system that is frankly nonnegotiable. What do I mean by that? Well, let's say that you were to wake up after six or eight hours of sleep and to drink a lot of caffeine and keep drinking caffeine throughout the day blocking those adenosine receptors. Yes, you'll offset fatigue. You'll offset sleepiness because that adenosine simply can't function.

40:27 But at the point where the caffeine becomes dislodged from the adenosine receptors, you will have a massive glut, a backlog of adenosine, and you will feel extra, extra sleepy. So really, there's no way to create more energy in your system. Really, what you're doing is you're changing the timing in which the sleepy signals and the more energetic signals are arriving. And this is really important to understand as the backdrop to the various tools that we're going to get into next, in which you can use caffeine for enhancing mental performance and physical performance and other aspects of health. But it's very important to understand this concept that, when you wake up in the morning provided that you slept well and enough the night before,

41:12 your levels of adenosine will be about as low as they will ever be. Actually, in order to get your adenosine levels really bottomed out, you want to avoid caffeine in the first 90 to 120 minutes after waking. We'll talk about why that is because it turns out there's a way to completely clear adenosine out of your system in the hour or so after waking. But for most people, adenosine levels are going to be close to their lowest after a good night's sleep. But there's really no negotiating the accumulation of adenosine that's going to occur and going to bias you towards feeling more sleepy than you would. Otherwise, that's going to occur throughout the day. There's really no way to eliminate adenosine. All you can really do is block its function. So it's sort of like borrowing energy against the fatigue that you will inevitably feel. Now this actually has a very important

41:57 socioeconomical relevance. Before caffeine was regularly consumed by human beings, we were really slaves to the light/dark cycle. And this was especially true before the presence of artificial lighting. But even before the advent of artificial lighting, humans were largely constrained to the outside light/dark cycle. We need to be active during the day and working during the day, and we need to be asleep at night. Caffeine allows us to divorce ourselves from that circadian cycle. Circadian just means about 24 hour. Caffeine allows us to do that at least somewhat by way of increasing our alertness. That is, spiking our alertness at various times throughout the day and even at night. This is how we can have shift workers, for instance,

42:43 that can sleep during the day and then drink a strong cup of coffee at 8:00 PM and then work into the night. That ability completely transformed our society. Now, of course, the healthiest schedule-- and we know this with certainty. The healthiest schedule for brain and body is going to be alert during the daytime and asleep at night. There's no question about that. Shift workers run into all sorts of health problems. And thank you shift workers for doing the important work that you do. We need you. Air traffic controllers, paramedics, firefighters, police officers, et cetera. But we know that there are serious health consequences, negative health consequences, that is, for shift workers. But for most people out there, about 95% of people follow a typical schedule. They're awake during the day and asleep at night. And yet it used to be before the advent of caffeine-containing beverages that, if you were

43:29 sleepy in the afternoon, you either had to take a nap or battle that sleepiness, that your activity rhythms and your sleep rhythms were governed by these circadian changes in availability of sunlight and when you slept. And you just didn't have the ability to ingest a beverage that would increase your levels of alertness because you block adenosine. So this is important to understand that, nowadays, we certainly live in a time in which we use-- in fact, 90% or more of adults and half or more of adolescents and teenagers use caffeine as a way to negotiate with, to borrow against this natural pattern of adenosine making us sleepy. But again, you're just offsetting the effects of sleepiness that adenosine causes.

44:15 You can't eliminate the adenosine entirely. The important point is that adenosine as a pro-sleep molecule is a nonnegotiable aspect of your biology. In fact, it's so nonnegotiable that, every 24 hours, you are going to release adenosine, and you're going to release adenosine in direct proportion to how long you've been awake. So the longer you've been awake, the more adenosine circulating in your system. There are really only a handful of ways to completely clear out adenosine. The major one being to get sleep. The other is to take a short nap, which, of course, is sleep, but it's shallow sleep. Or non-sleep deep rest, so-called NSDR, has been shown to reduce levels of adenosine. And there are certain things such as viewing morning sunlight, which because of its effects on cortisol,

45:01 can quote unquote, "clear out adenosine." We'll talk about this in more detail in a few minutes. And there's also evidence that certain forms of exercise, provided that it's brief and intense, can also reduce adenosine, not just block its effects. Now that we've talked about some of the incredible mechanisms by which caffeine changes our experience of life, increases alertness and mood, et cetera, I want to talk about the use of caffeine as a tool. Now caffeine is a very potent and useful tool for enhancing mental health, physical health, and performance. But there are certain considerations one has to keep in mind, in particular, dose. Now, first off, not everybody will respond to the same dose of caffeine the same way, but we can reliably say that your body weight is

45:47 a good measure by which you can estimate what a healthy, useful dose of caffeine would be. So for most people, ingesting 1 to 3 milligrams of caffeine per kilogram of body weight is going to be the range in which caffeine can have positive effects without making us feel overly anxious and give us that feeling that we're jumping out of our skin and turn the otherwise positive experience of caffeine into an aversive one. For those of you that aren't familiar with thinking in terms of kilograms and normally think in pounds, I'll just quickly give you some general estimations that, for instance, 100 kilograms equals 220 pounds. So for me, I weigh 100 kilograms. That means that 1 to 3 milligrams--

46:36 again, milligrams, thousandth of a gram. 1 to 3 milligrams of caffeine per kilogram of body weight would mean for me. I could safely ingest 100 to 300 milligrams of caffeine in a single dose, in a single drink, if that's the way I'm consuming it, or pill form if that's the way that I'm consuming it. And it's very likely that that will be a tolerable dose. However, if you are not somebody that's accustomed to drinking caffeine on a regular basis, I suggest you start on the lower end of that 1 to 3 milligrams per kilogram of body weight range. So for instance, if you're somebody who weighs 50 kilograms, that's approximately 110 pounds. And you would be pretty comfortable ingesting somewhere between 50 and 150 milligrams of caffeine.

47:23 So what I recommend is that people who are considering using caffeine as a tool or who are already ingesting caffeine, start to think about the dosage of caffeine that you are ingesting or plan to ingest and the timing in which you ingest that caffeine relative to certain tasks throughout your day, your waking, and your sleep. And we'll talk about that in just a moment. But the first step for you is to figure out how much you weigh in kilograms and then to go to that number of 1 to 3 milligrams of caffeine per kilogram of body weight. And that's a good range in which you might want to explore the use of caffeine in a single application, meaning a single dose. Now, I do realize that some people out there are drinking coffee all day long or having coffee in the morning and again in the afternoon.

48:09 What I'm referring to here is the ingestion of caffeine in a single bout, right? 1 cup of coffee or 2 cups of coffee, for instance, to achieve that 100 to 300 milligram range if that's what's appropriate for your body weight. But to avoid any confusion, when I talk about dosage of caffeine, what I'm really talking about is not the total amount of caffeine ingested per day. I'm talking about the total amount of caffeine ingested in one sitting or setting, that is. And if you're somebody who's drinking caffeine multiple times throughout the day, you can imagine-- for instance, let's say the appropriate dose for you in order to get an enhancement in mental performance or physical performance is 200 milligrams. And you are somebody who's doing some work in the morning, and you want to have that lift in the morning to be able to focus better.

48:55 And you're doing some physical exercise in the afternoon or vice versa that you would ingest 200 milligrams of caffeine at two separate times per day separated by about four hours. Now you don't have to separate them. You could put them two hours apart, for instance. But we'll talk about half-life of caffeine and so forth. Just keep in mind that, if you're ingesting 200 milligrams of caffeine and that's the appropriate dose for you based on your body weight and then you are ingesting another 200 milligrams of caffeine an hour later, you are effectively ingesting approximately 400 milligrams of caffeine, which is going to start exceeding the dose in which you can normally tolerate without feeling anxious and jittery. With all of that said, there is a range of tolerance for caffeine that's based on two things. One is a preexisting disposition that is whether or not

49:42 your genetics and nervous system and the backdrop of your life, how much stress you're experiencing tends to make you feel more anxious and alert and jittery before you ingest any caffeine. And the other is how so-called caffeine-adapted you are. We often hear about tolerance. Tolerance means something very specific. It's the ability to ingest more and more of something with a plateau that is a no increase or an actual reduction in the effectiveness of that thing. But here we're not really talking about tolerance to caffeine. What we're talking about is being caffeine-adapted. A simple way to understand whether or not your caffeine-adapted or not is that, if you drink caffeine and it tends to increase your heart rate and make you feel more alert and a bit more anxious, then chances are you are not caffeine-adapted, provided the amount of caffeine is within the healthy range

50:27 for you, that is, the ranges we talked about a moment ago. However, here's somebody who drinks caffeine and you actually feel alert and relaxed, chances are you are caffeine-adapted. And so at various times during today's episode, I'll talk about people who are caffeine-adapted and people who are not caffeine-adapted. We'll talk about the use of caffeine every other day. I know a few habitual caffeine drinkers including myself, just the simple mention of that probably sounds aversive. But there is actually great utility to using caffeine every other day as opposed to every day. But just keep in mind that some people will drink caffeine and not get much of a lift from it at all. Other people will drink caffeine, and they will feel extremely anxious even at dosages far lower than that 1 to 3 milligrams per kilogram of body weight range that I described a moment ago.

51:14 So you have to take into account individual differences. That said, 1 to 3 milligrams of caffeine per kilogram of body weight for a given sitting. For your morning coffee or your morning yerba maté tea is a good range from which to start. And I do encourage you to go online and look up the various beverages and foods that you might be eating that contain caffeine. For instance, some people are surprised to discover that the coffee that they get from some of the more standard popular vendors out there, the small coffee or the medium coffee, for instance, can contain as much as 400 to 600 milligrams of caffeine. And the large coffee that is often sold at those commercial vendors can contain as much as 1 gram, 1,000 milligrams, of caffeine.

52:00 Now you may be adapted to that such that it doesn't make you feel anxious, but if you wonder why you feel irritable and you get a headache when you don't get that caffeine or that amount of caffeine at precisely the time that you're used to getting it each day, that's because you are consuming quite large quantities of caffeine on a regular basis. So I do recommend whether or not you drink soda or coffee or tea that you figure out the source of that. OK, so figure out what vendor you purchase it from, what kind of coffee, and go online and spend a little bit of time because the information is out there to discover what levels of caffeine you're actually ingesting. Now if you happen to be ingesting more than 1 to 3 milligrams per kilogram of body weight of caffeine, that's not necessarily bad.

52:46 However, you do want to be careful about ingesting very high levels of caffeine over long periods of time in your life because there can be issues that start to arise. In particular, a bias towards higher levels of anxiety and depletion of certain electrolytes. Because caffeine is a diuretic can cause you to lose sodium and other things of that sort. And also just from simply a dependent standpoint, it does appear that if you ingest high levels of caffeine that is exceeding the dosages that normally you could get away with and get just as much mental-enhancing and physical-enhancing benefits that you can cause some disruption to the microvasculature. You can bias yourself towards headaches, anxiety attacks, and you can become actually quite irritable

53:31 when you're not getting those higher levels of caffeine. So I do encourage you to figure out not just what an appropriate caffeine dosage would be for you but also how much caffeine you might already be ingesting. The first tool I'd like to talk about is one that I've mentioned before on this podcast several times. And it's something that if you haven't heard of will be very useful to you. And if you have heard this tool before, I'm going to add some additional features to the description of this tool that should make this worthwhile for you as well. And that is to delay your caffeine intake to 90 to 120 minutes after waking up on most days. And I'll be very clear as to days in which you might want to ingest caffeine more closely to when you wake up. Why would you want to delay your caffeine intake to 90

54:19 to 120 minutes after waking? The answer to that is very simple. Many people wake up in the morning. They drink caffeine within 10, 20, 30, sometimes within 2 minutes of waking. And they feel more alert naturally. That makes sense because of the effects of caffeine in blocking the effects of adenosine that I talked about earlier and its effects on other neurotransmitter systems. But then what they find is that, in the early afternoon, in particular, after lunch, they experience a dramatic dip in their overall levels of energy, the so-called afternoon crash. And in most cases, the way they respond to that is to ingest more caffeine, which indeed can increase their levels of mood and alertness. However, as we'll soon talk about,

55:04 there is a problem with ingesting caffeine in the afternoon if it falls within 8 or 10 or dare I even say 12 hours of going to sleep. And that is, the caffeine ingested in the afternoon-- for most everybody, let's say for 95-plus percent of people-- disrupts the architecture and quality of their nighttime sleep. And I should say that it doesn't necessarily impact their ability to fall asleep and maybe even sleep through the night but that the depth and quality of that sleep is disrupted by consuming caffeine in the afternoon. A little bit later, I'll talk about how you can offset some of those negative effects if you absolutely require caffeine in the afternoon. But there's a huge advantage to restricting your caffeine intake to the early part of your day but not consuming caffeine within the first 90

55:52 to 120 minutes after waking. In fact, many people find that if they delay their caffeine intake to 90 to 120 minutes after waking up that they feel more alert in the morning, and they completely avoid that afternoon crash. Now that said, many people, including myself, do need a short nap or non-sleep deep rest or other form of relaxation for 10 to 30 minutes in the afternoon. That is natural and healthy. I'm not referring to the need for that when I refer to the so-called afternoon crash. What I'm talking about in the afternoon crash is a inability to recover energy and focus and a need to consume more caffeine just to make it through the afternoon. By delaying caffeine intake to 90 to 120 minutes after waking,

56:38 there are a couple of things that are accomplished. First of all, you offset that afternoon crash. And this is an effect that many people experience the very first time they start delaying their caffeine intake to 90 to 120 minutes after waking. And the reason this works so well is the following. As I mentioned earlier, adenosine is a molecule that builds up the longer that we are awake. It is a molecule that is reduced or cleared from our system by sleep. So when we emerge from sleep regardless of how long we've slept, our adenosine levels are lower than they were when we went to sleep the previous night. If you slept well enough and long enough, those adenosine levels can be very, very low, but they are never completely zero. When you wake up in the morning, even

57:24 if you're one of these people that springs out of bed and is ready to attack the day-- and here I'm certainly not describing myself. I'm not one of those people. I tend to wake fairly slowly. But if you're one of those spring up and attack the day or you're one of the people who moves more slowly into your day, regardless, there's still some residual adenosine in your system. And this is particularly the case if you did not get enough sleep or enough depth of sleep the night before. The correct ratio is a slow-wave sleep and rapid eye movement sleep. And for those of you interested in optimizing sleep, I'll just refer you to our master your sleep episode of the Huberman Lab podcast, the perfect your sleep episode of the Huberman Lab podcast. And we have a tool kit for sleep all of which are available, zero cost, time-stamped, et cetera at hubermanlab.com.

58:11 You wake up in the morning. And your adenosine levels are low, but they're not zero. And if you didn't sleep that well or deeply enough the night before, you're going to have more adenosine in your system.

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